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PMID: 11036021 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Fluoroquinolone resistance in clinical isolates of Streptococcus pneumoniae: contributions of type II topoisomerase mutations and efflux to levels of resistance.

Antimicrobial agents and chemotherapy ·Vol. 44 ·No. 11 ·2000-11-00 ·Pages 3049-54

Bast DJ, Low DE, Duncan CL, Kilburn L, Mandell LA, Davidson RJ, de Azavedo JC

Abstract

We report on amino acid substitutions in the quinolone resistance-determining region of type II topisomerases and the prevalence of reserpine-inhibited efflux for 70 clinical isolates of S. pneumoniae for which the ciprofloxacin MIC is >/=4 microgram/ml and 28 isolates for which the ciprofloxacin MIC is </=2 microgram/ml. The amino acid substitutions in ParC conferring low-level resistance (MICs, 4 to 8 microgram/ml) included Phe, Tyr, and Ala for Ser-79; Asn, Ala, Gly, Tyr, and Val for Asp-83; Asn for Asp-78; and Pro for Ala-115. Isolates with intermediate-level (MICs, 16 to 32 microgram/ml) and high-level (MICs, 64 microgram/ml) resistance harbored substitutions of Phe and Tyr for Ser-79 or Asn and Ala for Asp-83 in ParC and an additional substitution in GyrA which included either Glu-85-Lys (Gly) or Ser-81-Phe (Tyr). Glu-85-Lys was found exclusively in isolates with high-level resistance. Efflux contributed primarily to low-level resistance in isolates with or without an amino acid substitution in ParC. The impact of amino acid substitutions in ParE was minimal, and no substitutions in GyrB were identified.

MeSH Terms
Amino Acid Substitution Anti-Infective Agents/pharmacology Bacterial Proteins/genetics,physiology Biological Transport, Active Ciprofloxacin/pharmacology DNA Gyrase DNA Topoisomerase IV DNA Topoisomerases, Type II/genetics,physiology DNA-Binding Proteins/genetics,physiology Drug Resistance, Microbial/genetics Humans Microbial Sensitivity Tests Phenotype Streptococcus pneumoniae/drug effects,enzymology,genetics
Chemicals
Anti-Infective Agents Bacterial Proteins DNA-Binding Proteins Ciprofloxacin DNA Topoisomerase IV DNA Gyrase DNA Topoisomerases, Type II
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Bast D J
Department of Microbiology, Mount Sinai Hospital and Toronto Medical Laboratories, University Health Network, Toronto, Ontario, Canada.
Low D E
Duncan C L
Kilburn L
Mandell L A
Davidson R J
de Azavedo J C
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Article Info
Journal
Antimicrobial agents and chemotherapy
Abbr.
Antimicrob Agents Chemother
ISSN
0066-4804
DOI
10.1128/AAC.44.11.3049-3054.2000
Published
2000-11-00
Pages
3049-54
Language
English
Region
United States
NLM ID
0315061
PMCID
PMC101601
Subset
IM
External Links
PubMed source DOI: 10.1128/AAC.44.11.3049-3054.2000 PMC Full Text View journal details
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